THE IGLV3-21 LIGHT CHAIN ANALYSIS IN CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS.

[OBJECTIVE] to analyze the frequency of IGLV321 light chain expression in chronic lymphocytic leukemia (CLL) patients and correlate it with clinical outcome taking into account anamnestic exposure to the ionizing radiation (IR).

[METHODS] The study was performed in a group of 244 unselected CLL patients. The main group (n = 106) included84 cleanup workers of the Chornobyl NPP accident, 16 inhabitants of radionuclide contaminated areas and 6 evacuees. The group of comparison consisted of 138 IR nonexposed patients. The diagnosis of CLL was based on clinical history, lymphocyte morphology, and immunophenotypic criteria. The immunoglobulin light chain (IGLV)rearrangements were analyzed by Sanger sequencing using BIOMED2 protocol in 132 patients, and in 112 patientsthe IGLV321 chain presence was tested with real time PCR method. The immunoglobulin heavy chain variable (IGHV)gene mutational status, TP53 and SF3B1 mutations were studied by PCR followed by direct sequencing. Data wereanalyzed with the SPSS software package, version 20.0.

[RESULTS] Twenty four (9.8 %) IGLV321 positive cases were identified. Its frequency did not differ in the main group(6.5 %) and in the group of comparison (12.5 %), p = 0.087. In the main group, IGLV321 gene expression was determined exclusively among cleanup workers. IGLV321 positive patients and patients with expression of other IGLVgenes were comparable by gender, age, stage at diagnosis, but IGLV321+ cases more frequently had mutated (M) IGHVgenes (66.7 % vs 29.5 %; p = 0.0001) and coexpressed IGHV321 gene (37.5 % vs 3.2 %; p = 0.0001). A significantpredominance of SF3B1 gene mutations among IGHV321 positive cases (47.4 % vs 21.2 %; p = 0.017) was revealed,while the frequency of TP53 (p = 0.596) and NOTCH1 (p = 0.286) gene mutations did not differ depending on theexpression of IGLV genes. Among patients with M IGHV genes periods of progressionfree (87 mo. vs 156 mo. inIGLV321 cases; p = 0.009) and overall survival (106 mo. vs 167 mo., respectively; p = 0.021) were shorter inIGLV321 positive cases. It has been showed that Binet stage, age > 65 years, and GLV321 gene expression were powerful adverse prognostic factors for overall survival in CLL patients with M IGHV genes. Significant factors for predicting progressionfree survival were: Binet stage, IGLV321 gene expression and initial leukocytosis > 70 x 109/L. Thesedata were common to patients of both observed groups regardless of radiation anamnesis.

[CONCLUSIONS] Our data confirmed unfavourable prognostic value of IGLV321 for prediction of progressionfree survival and overall survival in CLL patients with M IGHV genes, regardless of radiation anamnesis.